Distinct impact of letermovir discontinuation on tacrolimus pharmacokinetics based on concomitant azole antifungal agent.

Abstract

Letermovir can effectively prevent clinically significant cytomegalovirus infections following allogeneic hematopoietic stem cell transplantation (HCT). Although some antifungal agents influence the pharmacokinetics of tacrolimus after the discontinuation of letermovir, the effect of posaconazole (PSCZ) has not been previously described. This study retrospectively evaluated the association between azole type and tacrolimus pharmacokinetics before and after discontinuation of letermovir prophylaxis. The analysis included 89 patients who underwent HCT at our hospital. In the PSCZ group, the tacrolimus concentration-to-dose (C/D) ratio after letermovir discontinuation was significantly higher than that observed before discontinuation (median 7.91 vs 6.50, P = 0.004). The fold-change in the C/D ratio (post-/pre-discontinuation) was significantly higher in the PSCZ group compared with the fluconazole group (median 1.23 vs 0.83, P = 0.003). These findings suggest that tacrolimus pharmacokinetics after letermovir discontinuation in HCT recipients vary depending on which concomitant azole antifungal agent is used. Furthermore, the tacrolimus C/D ratio could increase following letermovir discontinuation in patients receiving PSCZ. Careful monitoring of tacrolimus concentrations at letermovir discontinuation is crucial to avoid an unexpected reversal of tacrolimus concentrations and prevent adverse events.